Latest Articles of Bioorganic & Medicinal Chemistry


Development of concise two-step catalytic approach towards lasofoxifene precursor nafoxidine 10.1016/j.bmc.2018.04.021 2018-04-10 We have elaborated a two-step catalytic approach to nafoxidine, a key precursor to lasofoxifene. Firstly, an efficient α-arylation of 6-methoxy-3,4-dihydronaphthalen-1(2H)-one with chlorobenzene was developed, which operates at low 0.1 mol% Pd-132 catalyst lo...
Substituent effect of N-benzylated gramine derivatives that prevent the PP2A inhibition and dissipate the neuronal Ca2+ overload, as a multitarget strategy for the treatment of Alzheimer’s disease 10.1016/j.bmc.2018.04.019 2018-04-09 Following the premises of the multitarget-directed ligands approach for the drug R&D against neurodegenerative diseases, where Alzheimer’s disease (AD) outstands, we have synthesized and evaluated analogues of the gramine derivative ITH12657 (1-benzyl-5-methy...
Rational Design and Screening of Peptide-Based Inhibitors of Heat Shock Factor 1 (HSF1) 10.1016/j.bmc.2018.04.018 2018-04-07 Heat shock factor 1 (HSF1) is a stress-responsive transcription factor that regulates expression of protein chaperones and cell survival factors. In cancer, HSF1 plays a unique role, hijacking the normal stress response to drive a cancer-specific transcriptio...
Characterization of Protease-Activated Receptor (PAR) ligands: Parmodulins are reversible allosteric inhibitors of PAR1-driven calcium mobilization in endothelial cells 10.1016/j.bmc.2018.04.016 2018-04-06 Several classes of ligands for Protease-Activated Receptors (PARs) have shown impressive anti-inflammatory and cytoprotective activities, including PAR2 antagonists and the PAR1-targeting parmodulins. In order to support medicinal chemistry studies with hundr...
Screening of ligands for redox-active europium using magnetic resonance imaging 10.1016/j.bmc.2018.04.001 2018-04-04 We report a screening procedure to predict ligand coordination to EuII and EuIII using magnetic resonance imaging in which bright images indicate complexation and dark images indicate no complexation. Here, paramagnetic GdIII is used as a surrogate for EuIII ...
Site-Specific Incorporation of Quadricyclane into a Protein and Photocleavage of the Quadricyclane Ligation Adduct 10.1016/j.bmc.2018.04.009 2018-04-04 The quadricyclane (QC) ligation is a bioorthogonal reaction between a quadricyclane moiety and a nickel bis(dithiolene) derivative. Here we show that a QC amino acid can be incorporated into a protein site-specifically using the pyrrolysine-based genetic code...
Structure-Based Design and Synthesis of 1H-pyrazolo[3,4-d]pyrimidin-4-amino Derivatives as Janus Kinase 3 Inhibitors 10.1016/j.bmc.2018.04.005 2018-04-04 Janus kinases (JAKs) regulate various inflammatory and immune responses and are targets for the treatment of inflammatory and immune diseases. Here we report the discovery and optimization of 1H-pyrazolo[3,4-d]pyrimidin-4-amino as covalent JAK3 inhibitors tha...
Synthesis and inhibitory activity of mechanism-based 4-coumaroyl-CoA ligase inhibitors 10.1016/j.bmc.2018.04.006 2018-04-04 4-Coumaroyl-CoA ligase (4CL) is ubiquitous in the plant kingdom, and plays a central role in the biosynthesis of phenylpropanoids such as lignins, flavonoids, and coumarins. 4CL catalyzes the formation of the coenzyme A thioester of cinnamates such as 4-couma...
Discovery and Evaluation of nNav1.5 Sodium Channel Blockers with Potent Cell Invasion Inhibitory Activity in Breast Cancer Cells 10.1016/j.bmc.2018.04.003 2018-04-03 Voltage-gated sodium channels (VGSC) are a well-established drug target for anti-epileptic, anti-arrhythmic and pain medications due to their presence and important roles that they play in excitable cells. Recently, their presence has been recognized in non-e...
Design and discovery of thioether and nicotinamide containing sorafenib analogs as multikinase inhibitors targeting B-Raf, B-RafV600E and VEGFR-2 10.1016/j.bmc.2018.03.039 2018-04-03 New sorafenib derivatives containing thioether and nicotinamide moiety were designed and synthesized as B-Raf, B-RafV600E and VEGFR-2 multikinase inhibitors. Their in vitro enzymatic inhibitory activities against B-Raf, B-RafV600E and VEGFR-2 and their antipr...

Development of concise two-step catalytic approach towards lasofoxifene precursor nafoxidine

10.1016/j.bmc.2018.04.021

2018-04-10

We have elaborated a two-step catalytic approach to nafoxidine, a key precursor to lasofoxifene. Firstly, an efficient α-arylation of 6-methoxy-3,4-dihydronaphthalen-1(2H)-one with chlorobenzene was developed, which operates at low 0.1 mol% Pd-132 catalyst lo...

Substituent effect of N-benzylated gramine derivatives that prevent the PP2A inhibition and dissipate the neuronal Ca2+ overload, as a multitarget strategy for the treatment of Alzheimer’s disease

10.1016/j.bmc.2018.04.019

2018-04-09

Following the premises of the multitarget-directed ligands approach for the drug R&D against neurodegenerative diseases, where Alzheimer’s disease (AD) outstands, we have synthesized and evaluated analogues of the gramine derivative ITH12657 (1-benzyl-5-methy...

Rational Design and Screening of Peptide-Based Inhibitors of Heat Shock Factor 1 (HSF1)

10.1016/j.bmc.2018.04.018

2018-04-07

Heat shock factor 1 (HSF1) is a stress-responsive transcription factor that regulates expression of protein chaperones and cell survival factors. In cancer, HSF1 plays a unique role, hijacking the normal stress response to drive a cancer-specific transcriptio...

Characterization of Protease-Activated Receptor (PAR) ligands: Parmodulins are reversible allosteric inhibitors of PAR1-driven calcium mobilization in endothelial cells

10.1016/j.bmc.2018.04.016

2018-04-06

Several classes of ligands for Protease-Activated Receptors (PARs) have shown impressive anti-inflammatory and cytoprotective activities, including PAR2 antagonists and the PAR1-targeting parmodulins. In order to support medicinal chemistry studies with hundr...

Screening of ligands for redox-active europium using magnetic resonance imaging

10.1016/j.bmc.2018.04.001

2018-04-04

We report a screening procedure to predict ligand coordination to EuII and EuIII using magnetic resonance imaging in which bright images indicate complexation and dark images indicate no complexation. Here, paramagnetic GdIII is used as a surrogate for EuIII ...

Site-Specific Incorporation of Quadricyclane into a Protein and Photocleavage of the Quadricyclane Ligation Adduct

10.1016/j.bmc.2018.04.009

2018-04-04

The quadricyclane (QC) ligation is a bioorthogonal reaction between a quadricyclane moiety and a nickel bis(dithiolene) derivative. Here we show that a QC amino acid can be incorporated into a protein site-specifically using the pyrrolysine-based genetic code...

Structure-Based Design and Synthesis of 1H-pyrazolo[3,4-d]pyrimidin-4-amino Derivatives as Janus Kinase 3 Inhibitors

10.1016/j.bmc.2018.04.005

2018-04-04

Janus kinases (JAKs) regulate various inflammatory and immune responses and are targets for the treatment of inflammatory and immune diseases. Here we report the discovery and optimization of 1H-pyrazolo[3,4-d]pyrimidin-4-amino as covalent JAK3 inhibitors tha...

Synthesis and inhibitory activity of mechanism-based 4-coumaroyl-CoA ligase inhibitors

10.1016/j.bmc.2018.04.006

2018-04-04

4-Coumaroyl-CoA ligase (4CL) is ubiquitous in the plant kingdom, and plays a central role in the biosynthesis of phenylpropanoids such as lignins, flavonoids, and coumarins. 4CL catalyzes the formation of the coenzyme A thioester of cinnamates such as 4-couma...

Discovery and Evaluation of nNav1.5 Sodium Channel Blockers with Potent Cell Invasion Inhibitory Activity in Breast Cancer Cells

10.1016/j.bmc.2018.04.003

2018-04-03

Voltage-gated sodium channels (VGSC) are a well-established drug target for anti-epileptic, anti-arrhythmic and pain medications due to their presence and important roles that they play in excitable cells. Recently, their presence has been recognized in non-e...

Design and discovery of thioether and nicotinamide containing sorafenib analogs as multikinase inhibitors targeting B-Raf, B-RafV600E and VEGFR-2

10.1016/j.bmc.2018.03.039

2018-04-03

New sorafenib derivatives containing thioether and nicotinamide moiety were designed and synthesized as B-Raf, B-RafV600E and VEGFR-2 multikinase inhibitors. Their in vitro enzymatic inhibitory activities against B-Raf, B-RafV600E and VEGFR-2 and their antipr...